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NEVROLOGICHESKIY ZHURNAL, № 3, 2016 DOI 10.18821/1560-9545-2016-21-3-165-167
CLINICAL RESEARCHES AND CASE REPORTS
© КОЛЛЕКТИВ АВТОРОВ, 2016 УДК 616.832-002-053.2-07
Voytenkov V.B.1, Skripchenko N.V.1, Zueva Y.E.2, Klimkin A.V.1, Skripchenko E.Y.3
functional state of motor neurons and its evaluation by transcranial magnetic stimulation in children with inflammatory lesions of the brain
'Scientific Research Institute of Children's Infections, 197022, Professora Popova, 9, Saint-Petersburg, Russia; e-mail: vlad203@ inbox.ru; 2Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel, 44837, Israel 3State budget institution of higher professional education Saint-Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, Saint-Petersburg, Russian Federation
Aim of study was to evaluate functional state of central nervous system motoneurons in patients with inflammatory disseminated small lesions of the brain. Methods: 20 controls (11 boys, 9 girls, mean age 15 years) and 32 patients with ADEM (n = 17) and MS (n = 15) were enrolled. Diagnosis was established by MRI and thorough clinical investigation. Mean age of the group of children with ADEM and MS was 14 years, there were 14 boys & 18 girls. All patients underwent transcranial magnetic stimulation (TMS), single-pulse protocol. Results: TMS showed good tolerability in children with encephalomyelitis and multiple sclerosis. Central motor pathways in patients with relatively small disseminated (multiple sclerosis, ADEM) lesions demonstrated high durability and stable TMS parameters, perhaps due to neuroplasticity. In all groups MEP latencies and amplitudes were comparable with medical normative, there were no significant differences with the controls. But it have to be noted, that in children in both MS and ADEM groups elevation of MEP threshold was seen significantly more often, which may be interpreted as signs of abnormal lowered functional state of motoneurons. As non-invasive, sensitive and relatively safe method, TMS should be more often implemented into the diagnostic protocols in pediatrics.
Key words: TMS; functional state; brain lesions; acute disseminated encephalomyelitis; multiple sclerosis; children. For citation: Voytenkov V.B., Skripchenko N.V., Zueva Y.E., Klimkin A.V., Skripchenko E.Y. Functional state of motor neurons and its evaluation by transcranial magnetic stimulation in children with inflammatory lesions of the brain. Nevrologicheskiy zhurnal (Neurological Journal) 2016; 21 (3): 165-167 (Russian). DOI 10.18821/1560-9545-2016-21-3-165-167.
For correspondence: Voytenkov Vladislav Borisovich - MD, PhD, Head of the department of functional diagnostics, Scientific Research Institute of Children's Infections, 197022, Professora Popova, 9, Saint-Petersburg, Russia; e-mail: vlad203@inbox.ru Conflict of interests. Authors declare no conflict of interests.
Funding. Authors of this paper received no funding (grants etc.) for performing of their work.
Войтенков В.Б.1, Скрипченко Н.В.1, Zueva Y.E.2, Климкин А.В.1, Скрипченко Е.Ю.3 ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ МОТОНЕЙРОНОВ У ДЕТЕЙ С ВОСПАЛИТЕЛЬНЫМ ПОРАЖЕНИЕМ ГОЛОВНОГО МОЗГА И ЕГО ОЦЕНКА С ПОМОЩЬЮ ТРАНСКРАНИАЛЬНОЙ МАГНИТНОЙ СТИМУЛЯЦИИ
'ФГБУ Научно-исследовательский институт детских инфекций федерального медико-биологического агентства, 197022, Профессора Попова, 9, Санкт-Петербург, Россия; e-mail:vlad203@inbox.ru; 2Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel, 44837, Israel; 'Государственное бюджетное учреждение высшего профессионального образования Санкт-Петербургский государственный педиатрический медицинский университет Минздрава РФ, Санкт-Петербург, Россия
Целью работы была оценка функционального состояния мотонейронов центральной нервной системы у детей с диссеминированным мелкоочаговым поражением головного мозга воспалительного генеза. Материалы и методы: в исследование включены 20 пациентов группы сравнения (11 мальчиков, 9 девочек, средний возраст 15 лет) и 32 ребенка с установленным диагнозом рассеянного склероза (n = 15) или диссеминированного энцефаломиелита (n = 17). Диагноз подтверждался с помощью магнитно-резонансной томографии (МРТ) головного мозга и неврологического обследования. Средний возраст группы детей с поражением головного мозга составлял 14 лет, в группу входили 14 мальчиков и 18 девочек. Всем проводили диагностическую транскраниальную магнитную стимуляцию (ТКМС), протокол с однократными стимулами.
Результаты. Во всех группах пациенты хорошо перенесли исследование. Центральные моторные пути у пациентов всех групп показали устойчивость к патологическому процессу - показатели латентности, амплитуды вызванных моторных ответов достоверно между группами не отличались. Возможно, это может отражать активно текущие у детей процессы нейропластичности. Тем не менее группа как рассеянного склероза, так и диссеминированного энцефаломиелита достоверно отличалась от контрольной по показателю порога вызванного моторного ответа, который был достоверно выше. Это отражает снижение функциональной активности мотонейронов у данной группы пациентов. Как неинвазивный, безопасный и информативный метод диагностики ТКМС следует чаще применять в педиатрической неврологии.
Ключевые слова: транскраниальная магнитная стимуляция (ТКМС); функциональное состояние; острый деми-елинизирующий энцефаломиелит; рассеянный склероз; дети.
Для цитирования: Войтенков В.Б., Скрипченко Н.В., Zueva Y.E., Климкин А.В., Скрипченко Е.Ю. Функциональное состояние мотонейронов у детей с воспалительным поражением головного мозга и его оценка с помощью транскраниальной магнитной стимуляции. Неврологический журнал 2016; 21 (3): 165-167 (Russian). DOI 10.18821/1560-9545-2016-21-3-165-167. Для корреспонденции: Войтенков Владислав Борисович, к.м.н., зав. отд. функциональных методов диагностики ФГБУ НИИ-ДИ ФМБА России. 197022, Санкт-Петербург, ул. Профессора Попова, 9. e-mail: vlad203@inbox.ru
Received 06.01.16 Accepted 27.05.16
НЕВРОЛОГИЧЕСКИЙ ЖУРНАЛ, № 3, 2016
DOI 10.18821/1560-9545-2016-21-3-165-167
КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ И НАБЛЮДЕНИЯ
Introduction. Lesions of central motor pathways of different origin (i.e. inflammation, tumors, vascular) lead to the impairment of motor function. Such impairment most commonly takes form of paresis on the contralateral side of the central lesion. In simplified view, this paresis extent has to reflect the size of the lesion. Nevertheless, in different patients same-size lesions of motor cortex or motor pathways presents differently. Main mechanism behind different deficit in different patients is neuroplas-ticity [8]. Neuroplasticity is a complex phenomenon, which may be characterized as the potential of the nervous system to reshape itself after injuries of different nature. Neuroplasticity may significantly differ according to the ongoing process of cerebral damage. Better compensation is usually observed in the case of slowly growing lesions, i.e. brain tumors, abscesses etc. Neuroplasticity as a phenomenon is not limited to the central nervous system, it is well described in a peripheral nerves as well [9].
Best neurophysiologic tool to evaluate different aspects of neuroplasticity is transcranial magnetic stimulation (TMS). TMS can be used in all age groups, including newborns, it's safe and effective [7]. TMS can provide a controlled and quantifiable input that can be matched across individuals of different ages and with different kind of lesions and disorders [3]. To directly assess neuroplasticity, paired-pulse stimulation is needed; but measurement of motor evoked potential's threshold may provide information on functional state of motoneurons and, indirectly, on neuroplasticity process in the brain [3].
Motor evoked potentials (MEPs), induced by TMS, are measured and registered using electromyography (EMG). Main MEP parameters are its latency, amplitude and shape. Central motor conduction time (CMCT) is also basic parameter, calculated during TMS analysis.
Aim of our study was to investigate central motor pathways in patients with disseminated relatively small lesions (patients with encephalitis and multiple sclerosis). By means of studying neuroplasticity and adaptation of patients to brain lesions, we implemented single-pulse TMS protocol.
Methods
20 controls (11 boys, 9 girls, mean age 15 years) and 32 patients with ADEM (n = 17) and MS (n = 15) were enrolled. Diagnosis was established by MRI and thorough clinical investigation. Mean age of the group of children with ADEM and MS was 14 years, there were 14 boys and 18 girls. Mean disease duration was 1,75 years ± 0,7 SD. TMS was performed according to currently accepted stan-
dard procedures. We used circular coil 90 mm and Neiro-MS-D magnetic stimulator, single-pulse TMS protocol.
Results
There were no adverse reactions, complaints or side-effects in both groups. TMS parameters, reflecting the conductivity along the motor pathways (MEPs latencies) of all groups are presented in Table 1.
Where MEPc med. D - cortical motor evoked potential from the right n. Medianus, MEPc med. S - motor evoked potential from the left n. Medianus (m. abductor pollicis brevis), MEPs - segmental (cervical) motor evoked potential; MEPc tib.D and S - cortical motor evoked potential from the right and left n. Tibialis (m. Abductor Hallucis), MEPs - segmental (lumbar) motor evoked potential; ADEM - acute disseminated encepha-lomyelitis.
As can be seen, in all groups MEP latencies were comparable with medical normative. Despite clear tendency towards longer latencies in ADEM and MS groups, there were no significant differences. Same findings were in amplitudes of MEPs (see Table 2).
Where MEPc med. D - cortical motor evoked potential from the right n. Medianus, MEPc med. S - motor evoked potential from the left n. Medianus (m. abductor pollicis brevis), MEPs - segmental (cervical) motor evoked potential; MEPc tib.D and S - cortical motor evoked potential from the right and left n. Tibialis (m. Abductor Hallu-cis), MEPs - segmental (lumbar) motor evoked potential; ADEM - acute disseminated encephalomyelitis.
There were also no statistically significant differences between controls and MS and ADEM patients on CMCT (see Table 3).
Where CMCT med. D - central motor conduction time when registered from the right n. Medianus, CMCT med. S - central motor conduction time when registered from the left n. Medianus (m. abductor pollicis brevis), CMCT tib.D and S - central motor conduction time when registered from the right and left n. Tibialis (m. Abductor Hal-lucis); ADEM - acute disseminated encephalomyelitis.
Abnormal findings in both groups with brain lesions were elevated MEP threshold (in 82% of the cases in MS patients and 75% in children with ADEM) and MEP shape changes (75% of the cases in MS patients and 83% of children with ADEM), this difference was significant when compared with controls. MEPs were polyphasic in all cases. In controls only 40% of the children had polyphasic MEPs; elevated threshold was registered in 30% of the cases (p < 0,05).
Table 1 (Табл. 1 )
Motor evoked potential's latency in children with multiple sclerosis, ADEM and controls
Латентность вызванных моторных ответов у детей с рассеянным склерозом, острым демиелинизирующим энцефаломиелитом и группы сравнения
Group MEPc med. MEPc MEPs MEPs MEPc tib.D, MEPc tib.S, MEPs tib.D, MEPs tib.S,
D latency, med.S, med.D, med.S, latency, ms latency, ms latency, ms latency, ms
ms latency, ms latency, ms latency, ms
Controls 21,37 ± 1,85 21,71 ± 1,38 11,22 ± 0,67 11,24 ± 0,72 36,73 ± 3,39 36,86 ± 3,36 20,01 ± 1,81 20,21 ± 0,91
Multiple 21,17 ± 3,24 20,88 ± 2,47 11,31 ± 0,87 11,28 ± 1,01 42,04 ± 4,81 42,075 ± 5,01 21,7 ± 2,61 21,75 ± 2,5
sclerosis
ADEM 20,31 ± 1,19 20,46 ± 2,12 11,19 ± 0,96 11,09 ± 1,04 40,25 ± 2,39 39,6 ± 2,94 22,06 ± 2,31 22,88 ± 2,1
NEVROLOGICHESKIY ZHURNAL, № 3, 2016 DOI 10 18821/1560-9545-2016-21-3-165-167
CLINICAL RESEARCHES AND CASE REPORTS
Table 2 (Табл. 2)
Motor evoked potential's amplitude in children with multiple sclerosis, ADEM and controls
Амплитуды вызванных моторных ответов у детей с рассеянным склерозом, острым демиелинизирующим энцефаломиелитом и группы сравнения
Group MEPc med. MEPc MEPs MEPs MEPc tib.D, MEPc tib.S, MEPs tib.D, MEPs tib.S,
D amplitude, med.S, am- med.D, am- med.S, am- amplitude, amplitude, amplitude, amplitude,
ms plitude, ms plitude, ms plitude, ms ms ms ms ms
Controls 2,84 ± 1,21 2,91 ± 1,02 9,37 ± 1,8 8,62 ± 1,65 1,52 ± 1,14 1,82 ± 1,09 5,97 ± 1,9 4,81 ± 1,63
Multiple 2,76 ± 1,72 2,89 ± 1,64 9,84 ± 2,27 8,32 ± 1,82 1,17 ± 0,58 1,24 ± 0,51 6,19 ± 2,81 6,59 ± 2,7
sclerosis
ADEM 3,08 ± 1,23 3,31 ± 1,54 9,07 ± 2,14 9,69 ± 1,38 1,65 ± 0,91 1,6 ± 0,94 8,71 ± 1,96 6,73 ± 1,64
Table 3 (Табл. 3)
Central motor conduction time in children with multiple sclerosis, ADEM and controls
Время центрального моторного проведения у детей с рассеянным склерозом, острым демиелинизирующим энцефаломиелитом и группой сравнения
Group
CMCT med. D, ms
CMCT med. S, ms
CMCT tib. D, ms
CMCT tib. S, ms
Controls
Multiple sclerosis ADEM
9,36 ± 1,43 9,64 ± 2,91 9,44 ± 1,81
9,07 ± 2,22 9,59 ± 2,98 9,29 ± 2,43
16,37 ± 1,27 19,81 ± 4,84 18,2 ± 2,69
16,23 ± 1,51 19,72 ± 5,21 16,95 ± 1,97
Discussion
Thus, children in both MS and ADEM groups showed signs of abnormal lowered functional state of motoneurons. MEP thresholds reflect mostly excitability of the cortical motor neurons, it may change during such tasks as motor imagery in brain-computer interface trained subjects [6]. It was suggested that elevated MEP threshold results from the altered membrane excitability of these neurons [2]. Polyphasic MEPs represents demyelination process in corticospinal tract, but may also be seen in healthy children under 18 years [5, 7].
Central motor pathways in both groups of children, with MS as well as with ADEM, demonstrated high durability towards lesions. Disseminated inflammation lesions failed to significantly alter CMCT, MEP latency and amplitudes. In our previous studies we have revealed changes of central inhibition in clinically diverse groups of patients, supposedly study of this design may be informative in future works in MS field [10].
Recovery and adaptation of central motor pathways may realize due to several mechanisms. One is reticulo-spinal pathway activation. This pathway is less developed in humans, than in primates, but in abnormal conditions its significance raises [1]. Rubrospinal, vestibulospinal and tectospinal tracts also start to play bigger roles during main motor pathways disruption [4]. Change of activity of previously spared motoneurons, cortical map remapping are also mechanisms involved in neuroplasticity in patients with different forms of CNS damage [8]. We propose that all these mechanisms take place in case of small disseminated brain lesions in children. But also our data may lead to suggestion on lowered functional state of the motoneu-rons in children with inflammatory lesions of the brain. This finding may be interpreted as sign of altered process of neuroplasticity in children with MS and ADEM.
Future investigations in this field have to include direct methods of brain plasticity assessment, i.e. paired-pulse transcranial magnetic stimulation.
Conclusions. TMS showed good tolerability in children with multiple sclerosis. Central motor pathways in patients with relatively small disseminated (multiple sclerosis, ADEM) lesions demonstrated high durability and stable TMS parameters, perhaps due to neuroplasti-city. But it have to be noted, that children in both MS and ADEM groups showed signs of abnormal lowered functional state of motoneurons. As non-invasive, sensitive and relatively safe method, TMS should be more often implemented into the diagnostic protocols.
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